The objective of this research is to improve treatment for cannabis dependent adults with comorbid major depression by augmenting depression pharmacotherapy with an innovative, integrated computer-assisted strategy combining the techniques of cognitive behavioral therapy and motivational enhancement therapy (CBT/MET) to promote relapse prevention skills, reduce cannabis use and depressive symptoms, and improve psychiatric treatment adherence. In 2007 the applicant received a Career Development Award to study an integrated CBT/MET intervention for the treatment of substance users with comorbid major depression in a primary mental health care setting. Results show that (a) cannabis dependence is among the most frequently observed addictive disorders among depressed adults in this setting; (b) integrating CBT/MET with psychiatric treatment for depression produces significant reductions in depressive symptoms and facilitates reductions in cannabis use that are comparable to those observed in psychosocial intervention studies targeting cannabis dependence. To extend this model of evidence-based psychotherapy implementation for depressed cannabis users receiving usual care (TAU) in a primary psychiatric care setting to a computer-based platform, the specific aims of this research are: 1) To conduct an RCT among 195 depressed, cannabis dependent adults receiving TAU, comparing computer-assisted, integrated CBT/MET (cICBT/MET) addressing cannabis use and depression, relative to therapist-delivered integrated CBT/MET (tICBT/MET) and TAU alone in improving cannabis use, depression, psychiatric treatment adherence, and healthcare outcomes; 2) To determine the cost-effectiveness of cICBT/MET; and 3) To examine neurobehavioral predictors and mechanisms of action of cICBT/MET, including impulsivity, operationalized by delay discounting, and self-efficacy. We hypothesize that cICBT/MET will yield superior clinical outcomes relative to TAU in reducing substance use, improving depressive symptoms and psychiatric treatment adherence, and reducing health service utilization during and after treatment. Moreover, we expect that cICBT/MET will be less costly and at least as effective as cICBT/MET. Further, we expect that cICBT/MET will have a direct effect on psychological variables that are recognized mechanisms of change in CBT and MET, and these changes will be associated with cannabis use and depression outcomes. By providing support to maximize psychiatric treatment adherence, coupled with coping skills to prevent relapse, cICBT/MET may provide a promising, cost-effective, and easily deployable strategy for the treatment of depressed cannabis users.